Lung injury from 02 toxicity is an important clinical problem. The mechanisms underlying 02 induced lung injury are unknown but very likely involve activated 02 byproducts and phagocytes. Phagocytes make large amounts of the 02 byproducts which could damage the lung directly. In addition, high 02 or 02 byproducts could damage the phagocytes themselves causing them to release toxic enzymes which injure the lung. Moreover, we found that high 02 causes macrophages to release factors which attract neutrophils thereby implicating macrophages in the recruitment of the increased phagocytes seen in 02 exposed lungs. Our objectives are to elucidate the roles of phagocytes in 02 induced lung injury. We will administer 100% 02 to rabbits for 24, 48, or 72 hours. Then, we will determine the time course relationships between the presence in lung lavages of: 1) macrophage deprived chemotactic factors, 2) the numbers of macrophages and neutrophils, 3) the metabolic and enzymatic activities of the retrieved phagocytes, and 4) activated 02 metabolites (malondialdeyde)and protective or toxic enzymes (SOD, catals, glutathione peroxidase, alpha-1-antitrypsin or proteolytic elastases) which may have come from phagocytes as a result of activation, lysis, and/or 100% 02. We will correlate these findings with the lung pathology and survival of the rabbits. We will also determine the effect on the above of interventions designed to alter the numbers, types, and/or activities of the lung phagocytes. We will decrease phagocytes by pretreating rabbits with nitrogen mustard or other agents. We will increase phagocytes by injecting inflammogens intratracheally. We will also transfuse phagocyte-depleted rabbits with control or experimentally altered phagocytes to see if we can alter the course of 02 induced lung injury. The results will provide new and needed information about the recruitment, activation and consequences of phagocytes in 02 induced lung injury. Since phagocytes are centrally involved in a number of lung disorders and because 02 toxicity resembles many other pulmonary diseases, the insights gained in this investigation should be widely applicable to lung and other diseases mediated by abnormalities of macrophage and/or neutrophil function.